ID - Transplant Flashcards
(49 cards)
Immune defects associated with these malignancy (and their therapies)
- AML, MDS
- Aplastic anaemia
- CLL and MM
- Lymphoma
- AML, MDS
– Qualitative/quantitative neutropenia - Aplastic anaemia
– Severe, prolonged neutropenia - CLL and MM
– Hypogammaglobulinemia - Lymphoma
– Functional asplenia
Consequence of chemo impacting neutrophils?
Cytotoxic agents
–> bacterial, fungal infection
Cancer drugs -> T cells impact ?
Consequences?
Purine analogues – Fludarabine, cladribine
Antithymoctye globulin
CD4+ T cell dysfunction:
* Herpes viruses
* Hep B reactivation
* PJP
What does s. pneumonia look like in microscopy
diplococci
Classic presentation of S Viridans in HIV patient
fevers, rash and stomatitis (think where it lives)
Associated with Viridans Group Strep (VGS) shock syndrome
– about 24-48 hr in 1/3 of cases
– Can have ARDS in ¼ of cases (like TSS)
- Endocarditis rare
RFs S Viridans in HIV
neutropenia, mucositis, high-dose cytarabine– use of Cipro (Cipro barely gets above MIC to be effective Gram Positive abx)
Neutropenic Enterocolitis (Typhlitis)
- Necrotizing inflammation with transmural infection of damaged bowel wall
- Mixed infection – GN, GP, anaerobic
- Can be accompanied by bacteremia
- Medical Management (less often surgical)
Mgmt Neutropenic Enterocolitis
Medical Management (less often surgical)
Skin lesion caused by pseudomonas aeriginosa?
erythema gangrenosum
Timing of fungal infections in neutropaenia
yeasts early (candida), mould later (aspergillus)
Difference between yeasts and moulds?
(and examples of each)
moulds: multicellular hyphae
- e.g. aspergillus, fusarium
Yeasts: single celled forms that reproduce by budding
- e.g. candida, cryptococcus,
Dimorphic exist also (Yeast in blood, but grow as mould in room temperatures)
- e.g. histoplasma, penicillium
How to anti-fungals usually work?
usually act on cell wall,
- exception if 5-FC which is converted to 5-FU and inhibits DNA synthesis (pyramidine analogue)
Anti-fungal for prophylaxis in high/ intermediate risk haem amlignancy/ HSCT?
Posaconazole in high risk
Fluconazole in Intermediate risk
What is the most rapidly cidal agent for Candida?
Caspofungin (the penicillin of anti-fungals)
Anti-fungal agent ineffective in cryptococcus?
Caspofungin
Cryptococcus (Zygomycetes) lack significant beta-glucan in their cell walls
Anti-fungal agent that covers everything?
posaconazole
Anti-fungal agent ineffective in moulds?
fluconazole (also flucytosine)
Important non-medical management candidaemia
MUST REMOVE IV LINES, dilated Eye exam
What is the most rapidly cidal agent for Aspergillus?
Voriconazole
Agents for cryptococcus
Flucytosine with Ampho
Hepatosplenic Candidiasis Syndrome
- Inflammatory response to fungi invaded by portal vasculature
- Presents after engraftment (Return of ANC)
- Abdominal pain, increased LFTs, prolonged fever
- Differential – bacteria, lymphoma, fungus
- C albicans most common
Lots of little abscesses in spleen/ liver after white cells returned and body sees all the things again
When to think invasive molds
- With profound neutropenia < 100 cells/mm 3 and >10-15 days)
- Most common AML – 20 x > than seen with lymphoma/
- Evidence of Sinusitis
or - Radiographic evidence of Evidence of Pulmonary disease
- If patient has received Fluconazole prophylaxis before.
Diagnosis of invasive moulds
- We rarely make diagnosis now by culture – usually inferred through molecular tests AND CT scan findings:
- (1–3)-beta-D-glucan test – Candida/Aspergillus/Fusarium (NOT Crypto/Zygomycetes)
– 60-90% sensitive - Galactomannan assay – only picks up aspergillus/penicillium –may have a role in BAL fluid in high risk patients – better sensitivity then culture (80 vs 50%)
- they both have a poor NPV
- PCR of BAL + GM diagnosis of proven/probable IPA were 90.2% and 96.4%.
Invasive aspergillosis treatment
– Voriconazole – PREFERRED
* Follow levels (>2 mg/L favourable response)
* Response is decrease Aspergillus galactomannan level
– No role for combination anti-fungals
– Reduce immunosuppression if possible
– Treatment duration
N Engl J Med, Vol. 347, No. 6
- 6-12 weeks
- Until immune recovery
- Until resolution of disease
– Secondary prophylaxis for further intense immunosuppression
